Study uncovers role of a protein in myelin-forming cells

July 20, 2018

Myelin – a membrane produced by specialized glial cells – plays a critical role in protecting the fibers that help carry messages throughout the body. In the central nervous system, glial cells known as oligodendrocytes are responsible for producing myelin. New findings have uncovered the role of a protein known as PRMT5 in the production of myelin.

From infancy through adolescence, myelinating oligodendrocytes are generated in abundance in the human brain by progenitor cells in a process that is highly sensitive to hormones, nutrients, and environmental conditions. In the adult brain, these progenitors cells serve as a reservoir for the generation of new myelin in response to learning and social experiences, or to repair myelin loss after injury (e.g. after immune attack to myelin, as in multiple sclerosis).

The molecular mechanisms that generate myelin-forming oligodendrocytes are only partially understood. Scientists at the Advanced Science Research Center at The Graduate Center of the City University of New York have pinpointed PRMT5 as a protein that essentially acts as a traffic cop, allowing progenitor cells to become oligodendrocytes and stopping the biological signals that would interfere with myelin production. PRMT5 promotes new myelin formation by acting on histones (proteins bound to DNA) and placing marks, which preclude the formation of obstacles to the differentiation of progenitor cells.

Researchers used three methods to eliminate PRMT5 and determine its role in myelin production in laboratory mice. First, they used CRISPR genetic ablation to target and eliminate the gene that produces PRMT5. In the second cohort, they used a pharmacological inhibitor to block activity of the protein. In the final cohort, they studied a group of knock-out mice who were born without the PRMT5-producing gene.

In each case, removing or blocking PRMT5 resulted in reduced progenitor cell differentiation and death of the cells that were attempting to become myelin producers.

The researchers’ findings show that blocking lysine acetyltransferases can favor myelin formation and also overcome the effect of PRMT5 inhibitors. These findings could be critical to improving the survival of patients with malignancies that need to be treated with PRMT5 inhibitors.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers said the discovery is a major step toward understanding the mechanisms of myelin production and the potential for treating certain central nervous system diseases.